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人脂肪来源干细胞转分化后T3激素对雪旺样细胞中神经营养因子和髓鞘碱性蛋白的上调作用

Upregulation of Neurotrophic Factors and Myelin Basic Protein in Schwann-like Cells by T3 Hormone Following Transdifferentiation of Human Adipose-derived Stem Cells.

作者信息

Zarinfard Giti, Aliakbari Maryam, Asgari Vajihe, Razavi Shahnaz

机构信息

Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Int J Mol Cell Med. 2022;11(1):41-54. doi: 10.22088/IJMCM.BUMS.11.1.41. Epub 2022 Oct 3.

Abstract

Peripheral nerve regeneration is a complicated phenomenon. Thyroid hormones are known as critical regulators in the nervous system development. The Schwann cells have the regenerative potency in the peripheral nervous system. In this study, the human adipose-derived stem cells were assessed , for transdifferentiation potency into Shwann-like cells (SLCs) as a candidate source for clinical cell therapy, under the treatment of triiodothyronine (T3) hormone, and compared with the untreated cells. The cell viability rate, myelination and neurotrophic factors expression of SLCs were evaluated two weeks post- induction by MTT assay, immunocytochemistry and real-time RT-PCR techniques, respectively. The obtained results revealed a significant decrease in SLCs viability, compared to the adipose-derived stem cells (P < 0.001). Immunocytochemistry technique was applied to detect SLCs markers, such as S100β, GFAP and myelin basic proteins (MBP) in the presence and absence of T3 treatment. The results indicated that administering T3 can significantly increase the differentiation and myelination potency of SLCs (P < 0.01). The findings of real-time RT-PCR technique indicated that the expression of Schwann cells markers, MBP, brain-derived neurotrophic factor and glial cell-derived neurotrophic factor were upregulated significantly with T3 hormone administration in comparison with the untreated cells (P < 0.05). The SLCs were able to express the neurotrophic factors and myelination related genes in the presence of T3 hormone. Furthermore, T3 administration improved myelination potency of adipose-derived stem cells, . Further experiments are necessary to confirm the advantages of using a combination of autologous SLCs and T3 hormone for peripheral nerve injury recovery.

摘要

周围神经再生是一个复杂的现象。甲状腺激素是神经系统发育中的关键调节因子。雪旺细胞在周围神经系统中具有再生能力。在本研究中,评估了人脂肪来源干细胞在三碘甲状腺原氨酸(T3)激素处理下向雪旺样细胞(SLCs)转分化的能力,作为临床细胞治疗的候选来源,并与未处理的细胞进行比较。分别通过MTT法、免疫细胞化学和实时RT-PCR技术在诱导后两周评估SLCs的细胞活力率、髓鞘形成和神经营养因子表达。获得的结果显示,与脂肪来源干细胞相比,SLCs的活力显著降低(P < 0.001)。应用免疫细胞化学技术检测在有或无T3处理情况下SLCs的标志物,如S100β、GFAP和髓鞘碱性蛋白(MBP)。结果表明,给予T3可显著提高SLCs的分化和髓鞘形成能力(P < 0.01)。实时RT-PCR技术的结果表明,与未处理的细胞相比,给予T3激素后雪旺细胞标志物、MBP、脑源性神经营养因子和胶质细胞源性神经营养因子的表达显著上调(P < 0.05)。在T3激素存在的情况下,SLCs能够表达神经营养因子和与髓鞘形成相关的基因。此外,给予T3可提高脂肪来源干细胞的髓鞘形成能力。进一步的实验有必要确认使用自体SLCs和T3激素联合用于周围神经损伤恢复的优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa4/9653553/a24ee182b8f8/ijmcm-11-41-g001.jpg

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